A group of proteins called molecular chaperons is a multifunctional protein, which promotes the formation of the functional structures of other proteins or maintains these structures, promotes correct association, inhibits unnecessary aggregation, protects other proteins from degradation, and promotes secretion (Non-Patent Document 1). HSP90 is a molecular chaperon as abundant as approximately 1 to 2% of all intracellular soluble proteins and is however unnecessary for the biosynthesis of the majority of polypeptides, unlike other chaperon proteins (Non-Patent Document 1). Signaling-related factors (e.g., ERBB1/EGFR, ERBB2/HER2, MET, IGF1R, KDR/VEGFR, FLT3, ZAP70, KIT, CHUK/IKK, BRAF, RAF1, SRC and AKT), cell cycle regulators (e.g., CDK4, CDK6, Cyclin D, PLK1 and BIRC5), and transcriptional regulators (e.g., HIF-1α, p53, androgen receptor, estrogen receptor and progesterone receptor) are known as the main client proteins whose structure formation or stability is regulated by HSP90 through the interaction therebetween (Non-Patent Documents 2 and 3). HSP90 is deeply involved in cell proliferation or survival by maintaining the normal functions of these proteins. Furthermore, HSP90 is required for the normal functions of mutated or chimeric factors (e.g., BCR-ABL and NPM-ALK) which cause carcinogenesis or exacerbation of cancer. This indicates the importance of HSP90 particularly for processes such as carcinogenesis, cancer survival, growth, exacerbation and metastasis (Non-Patent Document 2).
The inhibition of the chaperon functions of HSP90 by specific inhibitors such as geldanamycin causes the inactivation, destabilization and degradation of the client proteins, resulting in induction of a halt in cell proliferation or apoptosis (Non-Patent Document 4). In terms of the physiological functions of HSP90, HSP90 inhibitors are characterized in that they can simultaneously inhibit a plurality of signaling pathways involved in cancer survival/growth. Thus, the HSP90 inhibitors can serve as drugs having extensive and effective anticancer activity. Moreover, from the findings that cancer cell-derived HSP90 has higher activity and higher affinity for ATP or inhibitors than those of normal cell-derived HSP90, it has been expected that the HSP90 inhibitors would serve as drugs having high cancer selectivity (Non-Patent Document 5). Currently, the clinical development of a plurality of HSP90 inhibitors as anticancer agents is ongoing. The most advancing geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is under development as single agents as well as under test on the combined use with various anticancer agents (Non-Patent Documents 3 and 4). However, the problems of 17-AAG, such as poor solubility, instability in solutions, low oral absorption and liver toxicity, have also been pointed out (Non-Patent Documents 4 and 5). Thus, a new type of HSP90 inhibitor has been desired. It has also been reported that HSP90 inhibitors not only have anticancer activity but also can serve as therapeutic agents for autoimmune disease, inflammatory disease, central nervous system disease (e.g., Parkinson's disease, Alzheimer's disease, and Huntington's disease), viral infections, cardiovascular disease, etc. (Non-Patent Documents 2 and 6).